Imaging untangles mystery of drug-addicted brain

Nuclear medicine neuroimaging technology is at the forefront of efforts to uncover the complex neurotransmission mechanisms involved in drug addiction, according to Dr. Nora D. Volkow, director of the National Institute on Drug Abuse.

"These imaging tools will allow us to investigate how genes affect protein expression, how protein expression affects neurobiology, how neurobiology affects behavior, and how that affects social interactions," Volkow said when delivering the Henry Wagner Lecture at the Society of Nuclear Medicine meeting in June.

Discovering how genes make people more vulnerable to or protected from drug addiction may lead to interventions that will better protect those at risk.

"Ultimately, predetermination does not mean predestination," she said.

Volkow's research has shown that the number of dopamine receptors in the brain is related to one's susceptibility to drug addiction. She and others have also shown that the number of dopamine sites is socially dependent. People who are properly nurtured and socially integrated seem to have more dopamine receptor sites, which make them less susceptible to addiction. Drugs by themselves are not sufficient to cause addiction. Biology, genetics, and certain environmental situations such as poverty can make people more vulnerable, she said.

Using carbon-11 raclopride with PET, Volkow and colleagues imaged drug addicts and normal controls who were exposed to Ritalin, a stimulant drug. Half the controls reported the experience as pleasurable, and more than 90% of the cocaine users said it was extremely pleasurable. Imaging revealed that the responses were directly related to the expression of dopamine receptors. Subjects who reported the experience as pleasant had a lower receptor availability. Those who described it as unpleasant had more receptors. In prior animal studies, researchers increased the dopamine receptors, and alcohol intake was reduced by 70%.

"We believe that low levels of receptors make people more vulnerable to taking drugs because the experience is pleasurable," she said.

But what causes people to have high or low levels of receptors? For many years, Volkow believed it was simply genes. But imaging technology has allowed researchers to look at the relationship between addiction and the environment. The environment produces neurobiological changes in the brain, she said. One of the most redundant findings in humans has been that poverty is an environmental predictor of drug abuse.

Research has shown that monkeys raised in isolation do not necessarily have a lower level of receptors, but in a group situation, the dominant monkey has higher levels of dopamine receptors. In self-administered cocaine experiments, the dominant animals did not administer cocaine to any significant level, while the subordinate animals administered high levels.

Volkow has also used imaging to investigate age-related changes in the dopamine system and their functional significance. Her work has documented that the loss of dopamine brain function with age in healthy subjects who have no evidence of neurological dysfunction is nonetheless associated with motor slowing and with changes in performance of cognitive tasks that involve executive functions. Her work now focuses on strategies to minimize the age-related losses in dopamine brain activity as a means to improve quality of life in the elderly.